ABSTRACT The proposed Behavioral Research project uses innovative approaches to address Hispanic cancer health disparities associated with the human papillomavirus (HPV). Persistent infection with HPV, the most common sexually-transmitted infection in the US, elevates the risk for multiple types of cancer. Vaccination against HPV is thus a critical factor in cancer prevention, yet vaccine uptake across the country remains low. In the majority- Hispanic population of El Paso County, Texas, in contrast, the rates of first-dose HPV vaccine uptake in adolescents are among the highest in the nation. This group has not been systematically investigated to determine specific facilitators and barriers that impact HPV vaccination rates. Moreover, little is known about vaccine uptake or HPV awareness in adults, providing an outstanding opportunity to focus on HPV and cancer prevention across the lifespan. The objective of this project is to assess HPV-related knowledge, attitudes and practices in a majority-Hispanic community sample, identify barriers and facilitators of vaccine uptake, and use targeted interventions to modify behavior in this underserved population. Our hypothesis is that increased vaccination, screening, and health literacy will reduce Hispanic cancer health disparities related to HPV infection. Results from the proposed studies will significantly advance the field and extend current knowledge on factors that influence vaccine acceptability. We will provide quantitative, high-resolution analyses of sociocultural and contextual variables that impede or facilitate receipt of the HPV vaccine. We focus on Hispanics, as this group exhibits increased morbidity and late-stage cancer presentation, but is underrepresented in studies that facilitate prevention and early diagnosis. Through our efforts, we will discover and begin to address specific and previously unknown barriers to vaccination, augment identified facilitators of vaccine uptake, and develop interventions that are readily deployable in other settings. The proposed project increases access to and participation in research by persons of predominantly Latino/a origin. The US-Mexico border is a unique and valuable setting in which to conduct this research, as members of our bi-national community are exposed to different health care standards and diverse sociocultural and other influences that impact medical decision-making. An additional strength of our program is our engagement of emerging healthcare providers, community health workers, and cancer survivors. Our observations are likely to generalize to other regions of the US with similar ethnic or sociocultural characteristics. Findings from our studies will inform the search for targeted approaches to improve HPV vaccine uptake and increase cancer prevention in our region and beyond.